The Effects of Orally Administered Calcium Pentosan Polysulfate on Inflammation and Cartilage Degradation Produced in Rabbit Joints by Intraarticular Injection of a Hyaluronate—Polylysine Complex

Smith, Margaret M.; Ghosh, Peter; Numata, Yukiko; Bansal, Mohinder K.

doi:10.1002/art.1780370118

Cited by 48 publications

(34 citation statements)

References 48 publications

(47 reference statements)

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“…26 Pentosan polysulfate is approved for the treatment of interstitial cystitis in the US, 3 but it is also an anti-osteoarthritic drug. 23,24,43 Apart from its antiinflammatory properties, 8,9,40,41,71,72,85 PPS is a potent leukocyte elastase 4 and aggrecanase (ADAMTS-4 and ADAMTS-5) inhibitor. [77][78][79][80] Pentosan polysulfate has been shown to mediate part of its antiinflammatory effects by downregulating TNF-a activity via the suppression of NF-Kb nuclear translocation and inhibition of the MAPKs pathways.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model

Oehme

Ghosh

Shimmon

et al. 2014

SPI

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Object Following microdiscectomy, discs generally fail to undergo spontaneous regeneration and patients may experience chronic low-back pain and recurrent disc prolapse. In published studies, formulations of mesenchymal progenitor cells combined with pentosan polysulfate (MPCs+PPS) have been shown to regenerate disc tissue in animal models, suggesting that this approach may provide a useful adjunct to microdiscectomy. The goal of this preclinical laboratory study was to determine if the transplantation of MPCs+PPS, embedded in a gelatin/fibrin scaffold (SCAF), and transplanted into a defect created by microdiscectomy, could promote disc regeneration. Methods A standardized microdiscectomy procedure was performed in 18 ovine lumbar discs. The subsequent disc defects were randomized to receive either no treatment (NIL), SCAF only, or the MPC+PPS formulation added to SCAF (MPCs+PPS+SCAF). Necropsies were undertaken 6 months postoperatively and the spines analyzed radiologically (radiography and MRI), biochemically, and histologically. Results No adverse events occurred throughout the duration of the study. The MPC+PPS+SCAF group had significantly less reduction in disc height compared with SCAF-only and NIL groups (p < 0.05 and p < 0.01, respectively). Magnetic resonance imaging Pfirrmann scores in the MPC+PPS+SCAF group were significantly lower than those in the SCAF group (p = 0.0213). The chaotropic solvent extractability of proteoglycans from the nucleus pulposus of MPC+PPS+SCAF-treated discs was significantly higher than that from the SCAF-only discs (p = 0.0312), and using gel exclusion chromatography, extracts from MPC+PPS+SCAF-treated discs also contained a higher percentage of proteoglycan aggregates than the extracts from both other groups. Analysis of the histological sections showed that 66% (p > 0.05) of the MPC+PPS+SCAF-treated discs exhibited less degeneration than the NIL or SCAF discs. Conclusions These findings demonstrate the capacity of MPCs in combination with PPS, when embedded in a gelatin sponge and sealed with fibrin glue in a microdiscectomy defect, to restore disc height, disc morphology, and nucleus pulposus proteoglycan content.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model

Oehme

Ghosh

Shimmon

et al. 2014

SPI

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“…In vitro studies have found that a combination of MPCs and PPS increases MPC viability and reduces apoptosis and TACE (ADAM-17) production while supporting proliferation and chondrogenic differentiation. 23 Furthermore, apart from its known antiinflammatory and anticomplement activities, [4][5][6]8,31,63 PPS can abrogate aggrecanase (ADAMTS-4 and ADAMTS-5) activity by increasing the extracellular levels of tissue inhibitor of matrix metalloproteinase 3 (TIMP-3). [66][67][68][69] There are several important limitations to this study.…”

Section: 6165mentioning

confidence: 99%

Reconstitution of degenerated ovine lumbar discs by STRO-3–positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate

Oehme

Ghosh

Goldschlager

et al. 2016

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OBJECTIVE Disc degeneration and associated low-back pain are major causes of suffering and disability. The authors examined the potential of mesenchymal precursor cells (MPCs), when formulated with pentosan polysulfate (PPS), to ameliorate disc degeneration in an ovine model. METHODS Twenty-four sheep had annular incisions made at L2–3, L3–4, and L4–5 to induce degeneration. Twelve weeks after injury, the nucleus pulposus of a degenerated disc in each animal was injected with ProFreeze and PPS formulated with either a low dose (0.1 million MPCs) or a high dose (0.5 million MPCs) of cells. The 2 adjacent injured discs in each spine were either injected with PPS and ProFreeze (PPS control) or not injected (nil-injected control). The adjacent noninjured L1–2 and L5–6 discs served as noninjured control discs. Disc height indices (DHIs) were obtained at baseline, before injection, and at planned death. After necropsy, 24 weeks after injection, the spines were subjected to MRI and morphological, histological, and biochemical analyses. RESULTS Twelve weeks after the annular injury, all the injured discs exhibited a significant reduction in mean DHI (low-dose group 17.19%; high-dose group 18.01% [p < 0.01]). Twenty-four weeks after injections, the discs injected with the low-dose MPC+PPS formulation recovered disc height, and their mean DHI was significantly greater than the DHI of PPS- and nil-injected discs (p < 0.001). Although the mean Pfirrmann MRI disc degeneration score for the low-dose MPC+PPS–injected discs was lower than that for the nil- and PPS-injected discs, the differences were not significant. The disc morphology scores for the nil- and PPS-injected discs were significantly higher than the normal control disc scores (p < 0.005), whereas the low-dose MPC+PPS–injected disc scores were not significantly different from those of the normal controls. The mean glycosaminoglycan content of the nuclei pulposus of the low-dose MPC+PPS–injected discs was significantly higher than that of the PPS-injected controls (p < 0.05) but was not significantly different from the normal control disc glycosaminoglycan levels. Histopathology degeneration frequency scores for the low-dose MPC+PPS–injected discs were lower than those for the PPS- and Nil-injected discs. The corresponding high-dose MPC+PPS–injected discs failed to show significant improvements in any outcome measure relative to the controls. CONCLUSIONS Intradiscal injections of a formulation composed of 0.1 million MPCs combined with PPS resulted in positive effects in reducing the progression of disc degeneration in an ovine model, as assessed by improvements in DHI and morphological, biochemical, and histopathological scores.

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“…Calcium (Ca) salts have anti-inflammatory activities (6,7), and various Ca salts have demonstrated preventive or therapeutic effects on osteoporosis (8,9). Polycan is purified β-glucan from Aureobasidium pullulans SM-2001, and is comprised mostly of β-1,3/1,6-glucan (10).…”

Section: Introductionmentioning

confidence: 99%

Effect of Polycalcium, a mixture of Polycan and calcium lactate-gluconate in a 1:9 weight ratio, on rats with surgery-induced osteoarthritis

Choi¹,

Shin²,

Kim³

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. In the present study, the beneficial and synergistic effects of Polycalcium, a mixture of Polycan and calcium (Ca) lactate-gluconate in a 1:9 weight ratio, on a rat model of osteoarthritis (OA) were explored. Polycalcium (50, 100 and 200 mg/kg) was administered orally once per day for 28 days from 1 week after the OA-modeling surgery. Diclofenac sodium (2 mg/kg) was administered as a reference drug. Following the OA surgery, increases in the maximum extension angles, edematous changes in knee and capsule thickness, reductions in chondrocyte proliferation and cartilage glycosaminoglycan (GAG) levels, as well as changes in cartilage degeneration were observed. However, these OA-related symptoms were inhibited after 28 days of continuous oral treatment with Polycalcium. Anti-OA effects, including the induction of chondrocyte proliferation, were detected in the Polycalcium-treated rats and were more favorable compared with those in rats treated with Polycan or Ca lactate-gluconate alone (100 mg). Therefore, a mixture of Polycan and Ca lactate-gluconate was demonstrated to have beneficial synergistic effects on OA.

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The Effects of Orally Administered Calcium Pentosan Polysulfate on Inflammation and Cartilage Degradation Produced in Rabbit Joints by Intraarticular Injection of a Hyaluronate—Polylysine Complex

Cited by 48 publications

References 48 publications

Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model

Mesenchymal progenitor cells combined with pentosan polysulfate mediating disc regeneration at the time of microdiscectomy: a preliminary study in an ovine model

Reconstitution of degenerated ovine lumbar discs by STRO-3–positive allogeneic mesenchymal precursor cells combined with pentosan polysulfate

Effect of Polycalcium, a mixture of Polycan and calcium lactate-gluconate in a 1:9 weight ratio, on rats with surgery-induced osteoarthritis

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